The overall objective of this research effort is to develop bioelastic nanoparticles for the delivery of vaccines. The nanoparticle is to function simultaneously as adjuvant and as a controlled release device capable, with a single administration, of achieving primary and follow on immunization by both immediate and sustained release of antigen. The C-fragment of tetanus toxin, Tox-C, will be the model antigen because of its low inherent immunogenicity, its pI of 5.1, and its importance in the world-wide tetanus health problem. The specific aims of this Phase I proposal are: 1) To design and prepare four elastic protein-based polymers using recombinant DNA technology for gene construction, E. coli transformation and expression, production by fermentation and purification. 2) To prepare bioelastic nanoparticles (200 nm or less) comprised of the four polymers. 3) To load the nanoparticles with the C-fragment of tetanus toxin (Tox-C). 4) To determine in vitro Tox-C release profiles for the nanoparticles, and 5) To evaluate efficacy in mice using two compositions with preferred release profiles and adjuvanticity. Further evaluation of different vaccine antigens and administration routes by means of in vivo animal model studies and the necessary steps toward clinical trials will be carried out during Phase II. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE